Dissolution testing is often performed as part of preparing and evaluating soluble materials, particularly pharmaceutical dosage forms (e.g., tablets, capsules, and the like) consisting of a therapeutically effective amount of active drug carried by an excipient material. Typically, dosage forms are dropped into test vessels that contain dissolution media of a predetermined volume and chemical composition. For instance, the composition may have a pH factor that emulates a gastro-intestinal environment. Dissolution testing can be useful, for example, in studying the drug release characteristics of the dosage form or in evaluating the quality control of the process used in forming the dose. To ensure validation of the data generated from dissolution-related procedures, dissolution testing is often carried out according to guidelines approved or specified by certain entities such as United States Pharmacopoeia (USP), in which case the testing must be conducted within various parametric ranges. The parameters may include dissolution media temperature, the amount of allowable evaporation-related loss, and the use, position and speed of agitation devices, dosage-retention devices, and other instruments operating in the test vessel.
As a dosage form is dissolving in the test vessel of a dissolution system, optics-based measurements of samples of the solution may be taken at predetermined time intervals through the operation of analytical equipment such as a spectrophotometer. The analytical equipment may determine analyte (e.g. active drug) concentration and/or other properties. The dissolution profile for the dosage form under evaluation—i.e., the percentage of analytes dissolved in the test media at a certain point in time or over a certain period of time—can be calculated from the measurement of analyte concentration in the sample taken. In one specific method employing a spectrophotometer, sometimes referred to as the sipper method, dissolution media samples are pumped from the test vessel(s) to a sample cell contained within the spectrophotometer, scanned while residing in the sample cell, and in some procedures then returned to the test vessel(s). In another more recently developed method, sometimes referred to as the in situ method, a fiber-optic “dip probe” is inserted directly in a test vessel. The dip probe includes one or more optical fibers that communicate with the spectrophotometer. In the in situ technique, the spectrophotometer thus does not require a sample cell as the dip probe serves a similar function. Measurements are taken directly in the test vessel and thus optical signals rather than liquid samples are transported between the test vessel and the spectrophotometer via optical fibers.
The apparatus utilized for carrying out dissolution testing typically includes a vessel plate having an array of apertures into which test vessels are mounted. When the procedure calls for heating the media contained in the vessels, a water bath is often provided underneath the vessel plate such that each vessel is at least partially immersed in the water bath to enable heat transfer from the heated bath to the vessel media. Alternatively, heating elements may be attached directly to the vessel. In one exemplary type of test configuration (e.g., USP-NF Apparatus 1), a cylindrical basket is attached to a metallic drive shaft and a pharmaceutical sample is loaded into the basket. One shaft and basket combination is manually or automatically lowered into each test vessel mounted on the vessel plate, and the shaft and basket are caused to rotate. In another type of test configuration (e.g., USP-NF Apparatus 2), a blade-type paddle is attached to each shaft, and the pharmaceutical sample is dropped into each vessel such that it falls to the bottom of the vessel. When proceeding in accordance with the general requirements of Section <711> (Dissolution) of USP24-NF19, each shaft must be positioned in its respective vessel so that its axis is not more than 2 mm at any point from the vertical axis of the vessel.
It is therefore a criterion in certain uses of vessels in which instruments operate that the vessel, and especially its inner surfaces, be aligned concentrically with respect to the instrument. Various approaches have been taken to assist in meeting this criterion, including those disclosed in U.S. Pat. No. 5,403,090, U.S. Pat. No. 6,562,301, U.S. Pat. No. 6,673,319, and U.S. Patent App. Pub. No. 2009/0208377, all assigned to the assignee of the present disclosure. Another approach to vessel alignment is disclosed in U.S. Pat. No. 5,589,649. Yet another approach to vessel alignment is the EaseAlign™ vessel centering ring commercially available from Varian, Inc., Palo Alto, Calif. In addition to concentricity, the verticality of the vessel has an effect on its proper alignment relative to instruments. In the present context, “verticality” generally refers to the precision with which the inside surface of the vessel is truly vertical, or the degree to which the inside surface is truly parallel with the central axis of the vessel or with an elongated instrument inserted into the vessel along the central axis. Regardless of the means taken to ensure that the vessel is concentrically positioned within the aperture of a vessel plate in which the vessel is mounted, if the vessel is not accurately vertical than it is still not aligned accurately. As a result, the inside surface of the vessel will not be precisely parallel with a shaft-based instrument that is intended to be inserted along the central axis of the vessel, and the radial distance between the shaft and the inside surface of the vessel will vary at different elevational points along the central axis and/or at different circumferential positions relative to the central axis.
Accordingly, there is a need for a vessel capable of providing accurate concentricity and verticality when mounted in a vessel supporting structure such as may be included in a dissolution testing apparatus.